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Antigenic peptide delivery to antigen-presenting cells using a CD40-coiled coil affinity-based platform

Nyesiga, Barnabas ; Hägerbrand, Karin LU ; Varas, Laura LU ; Gjörloff Wingren, Anette LU ; Ohlin, Mats LU orcid ; Ellmark, Peter LU and von Schantz, Laura LU (2025) In Drug delivery 32(1).
Abstract

Delivery of antigenic peptides to antigen presenting cells (APCs) such as dendritic cells (DCs) using monoclonal antibodies (mAbs) is an attractive approach to evoke antigen-specific T cell activation and improve drug efficacy. Peptide linkage to mAbs has previously been achieved through genetic fusion, chemical conjugation, nano-engineered platforms and high affinity peptides. In this study, we have developed a flexible antibody-peptide linking technology using oppositely charged coiled coil domains to non-covalently link peptides to mAbs. The technology comprises (1) an anti-CD40 mAb connected with negatively charged E domains and (2) an immunogenic OVA peptide (SIINFEKL) from ovalbumin used as a model antigenic peptide fused with... (More)

Delivery of antigenic peptides to antigen presenting cells (APCs) such as dendritic cells (DCs) using monoclonal antibodies (mAbs) is an attractive approach to evoke antigen-specific T cell activation and improve drug efficacy. Peptide linkage to mAbs has previously been achieved through genetic fusion, chemical conjugation, nano-engineered platforms and high affinity peptides. In this study, we have developed a flexible antibody-peptide linking technology using oppositely charged coiled coil domains to non-covalently link peptides to mAbs. The technology comprises (1) an anti-CD40 mAb connected with negatively charged E domains and (2) an immunogenic OVA peptide (SIINFEKL) from ovalbumin used as a model antigenic peptide fused with positively charged K domains. Combining these constructs leads to the formation of complexes that can be targeted to CD40 expressed on cells. Proof of concept antibody constructs connected with E domains generated from transient expressions exhibited good manufacturability, binding, and stability attributes comparable to a control mAb. Also, optimal repeat lengths for coiled-coil oligomerization domains were identified in these studies. Binding kinetics studies showed that connecting E domains to mAbs do not impede Fc gamma and neonatal receptor interactions. Additionally, formation of stable complexes capable of binding CD40 expressing cells was demonstrated in vitro. In vivo functionality evaluations showed that treatment of human CD40 transgenic mice with complexes elicited expansion of OVA peptide-specific CD8+ T cells and potent antitumor effects superior to peptide monotherapies. Overall, these findings demonstrate that the technology has great potential for application as an in vivo tool for antigenic peptide delivery.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
antigen presenting cells, CD40, coiled coil, dendritic cells, targeted delivery
in
Drug delivery
volume
32
issue
1
article number
2486340
publisher
Taylor & Francis
external identifiers
  • pmid:40417977
  • scopus:105006602919
ISSN
1071-7544
DOI
10.1080/10717544.2025.2486340
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 Alligator Bioscience AB, Sweden. Published by Informa UK Limited, trading as Taylor & Francis Group.
id
3dede2ca-ba63-42d9-94d2-be00297cfe4f
date added to LUP
2025-06-16 09:17:19
date last changed
2025-07-14 12:04:09
@article{3dede2ca-ba63-42d9-94d2-be00297cfe4f,
  abstract     = {{<p>Delivery of antigenic peptides to antigen presenting cells (APCs) such as dendritic cells (DCs) using monoclonal antibodies (mAbs) is an attractive approach to evoke antigen-specific T cell activation and improve drug efficacy. Peptide linkage to mAbs has previously been achieved through genetic fusion, chemical conjugation, nano-engineered platforms and high affinity peptides. In this study, we have developed a flexible antibody-peptide linking technology using oppositely charged coiled coil domains to non-covalently link peptides to mAbs. The technology comprises (1) an anti-CD40 mAb connected with negatively charged E domains and (2) an immunogenic OVA peptide (SIINFEKL) from ovalbumin used as a model antigenic peptide fused with positively charged K domains. Combining these constructs leads to the formation of complexes that can be targeted to CD40 expressed on cells. Proof of concept antibody constructs connected with E domains generated from transient expressions exhibited good manufacturability, binding, and stability attributes comparable to a control mAb. Also, optimal repeat lengths for coiled-coil oligomerization domains were identified in these studies. Binding kinetics studies showed that connecting E domains to mAbs do not impede Fc gamma and neonatal receptor interactions. Additionally, formation of stable complexes capable of binding CD40 expressing cells was demonstrated in vitro. In vivo functionality evaluations showed that treatment of human CD40 transgenic mice with complexes elicited expansion of OVA peptide-specific CD8+ T cells and potent antitumor effects superior to peptide monotherapies. Overall, these findings demonstrate that the technology has great potential for application as an in vivo tool for antigenic peptide delivery.</p>}},
  author       = {{Nyesiga, Barnabas and Hägerbrand, Karin and Varas, Laura and Gjörloff Wingren, Anette and Ohlin, Mats and Ellmark, Peter and von Schantz, Laura}},
  issn         = {{1071-7544}},
  keywords     = {{antigen presenting cells; CD40; coiled coil; dendritic cells; targeted delivery}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Taylor & Francis}},
  series       = {{Drug delivery}},
  title        = {{Antigenic peptide delivery to antigen-presenting cells using a CD40-coiled coil affinity-based platform}},
  url          = {{http://dx.doi.org/10.1080/10717544.2025.2486340}},
  doi          = {{10.1080/10717544.2025.2486340}},
  volume       = {{32}},
  year         = {{2025}},
}